Project Summary Most studies of behavioral impairments in aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD) focus on cognitive functions. Despite significant advances in our knowledge of the behavioral profile of AD over the last few decades, the current standard in neuropsychological testing has only modest reliability in diagnosing the disease in its earliest stages. Although diagnosis typically focuses primarily on cognitive function, recent research has emphasized the potential for measures of motor behavior to predict subsequent cognitive decline and development of MCI and AD. Recent work showed that memory declines in healthy aging contribute to impairments in motor learning, yet little is known about dysfunction of motor learning in MCI and AD. In particular, mathematical modeling has revealed that motor learning relies on a fast process that allows for rapid improvements in performance, and a slow process that leads to more gradual improvements. An important observation is that older adults with poor working memory performance exhibit impairments in motor learning, driven largely by changes in the fast process. The proposed research will leverage these recent advances in our knowledge of memory systems underlying motor learning to characterize group differences between younger and healthy older adults, MCI, and AD patients in the acquisition and long-term retention of motor skills. Aim 1 will characterize changes in the memory processes underlying short-term acquisition and retention of a novel motor skill in MCI and AD patients relative to healthy younger and older adults. Aim 2 will determine the impact of known impairments in long-term memory retention in MCI and AD on the long-term retention of a newly acquired motor skill. Aim 3 will demonstrate the utility of using a newly developed method of isolating different memory systems involved in motor learning for distinguishing between healthy aging, MCI, and AD. This final aim represents an important preliminary step towards the development of a motor learning task that could be adapted in the future for use in a clinical setting for diagnostic purposes. Our central hypothesis is that isolating the fast and slow memory contributions to motor learning will provide a sensitive way of distinguishing healthy aging from MCI and AD. This research is an important first step towards improving current clinical batteries aimed at early diagnosis of MCI and AD. Ultimately, discovering new behavioral markers that are sensitive to the earliest stages of AD will allow clinicians to maximize the benefits of currently available treatment options that can slow the progression of the disease and by extension, improve the quality of life of patients and their caregivers.